Combination of isocetyl stearoyl stearate and cetyl esters

Abstract

The present invention relates to a combination of isocetyl stearoyl stearate and cetyl esters or a cosmetic or dermatological composition comprising such a combination for use in enhancing the protection of the skin against allergens, in particular comprising heavy metals such as chromium and / or nickel.

Description

[0001] DESCRIPTION

[0002] TITLE: Association of isocetyl stearoyl stearate and cetyl esters

[0003] TECHNICAL FIELD OF THE INVENTION

[0004] The present invention relates to the use of an association of isocetyl stearoyl stearate and cetyl esters, and / or the use of a composition comprising an association of isocetyl stearoyl stearate and cetyl esters, to enhance the protection of the skin against allergens, in particular allergens comprising a metal.

[0005] STATE OF THE ART

[0006] The skin is one of the most important organs of the body, and is recognized as playing a major role in the immune system.

[0007] Heavy metals, particularly chromium and nickel, are commonly implicated in allergic contact dermatitis, skin inflammations resulting from delayed hypersensitivity.

[0008] Nickel allergy dermatitis is particularly widespread, manifesting as an immune reaction after skin contact, with symptoms such as erythema, edema, vesicles, and itching. This is an immune response of T lymphocytes following skin contact. Chronic exposure can lead to persistent dermatitis. Nickel is found in various alloys (stainless steel, etc.) used in coins, kitchen utensils, costume jewelry, automotive parts, and construction materials. Consequently, various professionals are exposed to this metal (hairdressers, mechanics, cashiers, shopkeepers, construction workers, etc.), but also in everyday life.

[0009] Chromium is frequently associated with occupational contact dermatitis, particularly in workers exposed to chromium cement. Allergic occupational dermatoses to chromium are primarily caused by hexavalent and trivalent chromium compounds, present in many alloys, cement, leather tanning agents, dyes, paint pigments, wood treatment products, and household products (detergents, dishwashing liquid, etc.). The most common occupational exposures come from wet cement containing hexavalent chromium and leather. The most exposed professions include construction, leather tanning, metallurgy, and those wearing leather protective equipment. Chromium contact dermatitis is most often scaly and cracked and localized to the hands and feet.Treating heavy metal allergic dermatitis requires a multidimensional approach including patient education, avoidance of exposure sources, the use of physical barriers (gloves, barrier creams, etc.) and topical treatments (corticosteroids). In severe cases, systemic therapy may be considered.

[0010] Prevention, particularly in high-risk occupational settings, is essential and involves safety standards, substitution with less allergenic materials, and training on safe handling practices.

[0011] Metal allergy dermatitis affects a significant portion of the population, with nickel allergies affecting up to 17% of women and 3% of men, and cobalt and chromium allergies affecting 1 to 3% of individuals (Thyssen and Menne 2010). Nickel and chromium are present in many products such as cement, paints, detergents, and everyday metal objects, and can therefore cause allergic reactions in sensitized individuals.

[0012] European standards limit the presence of nickel and chromium in certain products to reduce the risk of dermatitis. Research into understanding the immunological mechanisms and improving diagnostic and therapeutic measures is crucial to improving patients' quality of life.

[0013] It is therefore essential to strengthen the skin's protection against allergens, including heavy metals such as nickel or chromium.

[0014] SUMMARY OF THE INVENTION

[0015] The inventors have surprisingly demonstrated that a combination of isocetyl stearoyl stearate and cetyl esters significantly limits, and in particular synergistically limits, the absorption of chromium and / or nickel into the skin. This combination therefore protects the skin against allergens, especially contact allergens.

[0016] According to a first aspect, the invention relates to an association of isocetyl stearoyl stearate and cetyl esters for its use in strengthening the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0017] The invention also relates to the use, preferably non-therapeutic, particularly preferably cosmetic, of the combination of isocetyl stearoyl stearate and cetyl esters to enhance the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0018] The invention also relates to the use of the combination of isocetyl stearoyl stearate and cetyl esters for the preparation of a cosmetic or dermatological composition to enhance the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0019] The invention also relates to a method for strengthening the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel, comprising administering to a person in need an effective amount of a combination of isocetyl stearoyl stearate and cetyl esters.

[0020] According to a second aspect, the invention relates to a cosmetic or dermatological composition comprising isosocetyl stearoyl stearate and cetyl esters (composition according to the invention) for its use in strengthening the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0021] The invention also relates to the use, preferably non-therapeutic, particularly preferably cosmetic, of a composition according to the invention to enhance the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0022] The invention also relates to the use of a composition according to the invention for the preparation of a drug to enhance the protection of the skin against allergens (typically contact allergens), in particular allergens (typically contact allergens) comprising a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0023] The invention also relates to the use of a composition comprising isosocetyl stearoyl stearate and cetyl esters (and advantageously at least one cosmetically or dermatologically acceptable excipient) for the preparation of a cosmetic or dermatological composition to enhance skin protection against allergens (typically contact allergens), particularly allergens (typically contact allergens) containing a metal, and more particularly a heavy metal such as chromium and / or nickel. The invention further relates to a method for enhancing skin protection against allergens (typically contact allergens), particularly allergens (typically contact allergens) containing a metal, and more particularly a heavy metal such as chromium and / or nickel, comprising administering to a person in need an effective amount of a composition according to the invention.

[0024] Advantageously, the composition according to the invention will further comprise at least one cosmetically or dermatologically acceptable excipient.

[0025] DETAILED DESCRIPTION OF THE INVENTION

[0026] Definitions

[0027] In this description, "approximately" means that the value in question may be 10% lower or higher, in particular 5%, and especially 1%, than the stated value. "Topical application" in the context of this invention means application to the skin (including the scalp) and mucous membranes, preferably the skin.

[0028] For the purposes of this invention, "cosmetically or dermatologically acceptable" means something useful in the preparation of a cosmetic or dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable, and which is acceptable for cosmetic or dermatological use, in particular by topical application to the skin.

[0029] For the purposes of this description, "allergen" means a substance capable of causing an allergic reaction in a person when they come into contact with it.

[0030] For the purposes of this description, "contact allergen" means a substance capable of causing an allergic reaction in a subject through skin contact.

[0031] For the purposes of this invention, "heavy metal" means a metallic element with a density greater than 5 g / cm³ 3For the purposes of this description, the following metals are considered heavy metals: antimony (Sb), arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), tin (Sn), manganese (Mg), mercury (Hg), nickel (Ni), lead (Pb), selenium (Se), tellurium (Te), thallium (Tl), vanadium (V), and zinc (Zn). This will refer more specifically to chromium and / or nickel.

[0032] Isocetyl stearoyl stearate is the INCI name for the compound with the IUPAC name 14-methylpentadecyl 12-octadecanoyloxyoctadecanoate (CAS No. 97338-28-8), also known as isohexadecyl 12-[(l-oxooctadecyl)oxy]octadecanoate. It has the following formula:

[0033] Cetyl esters

[0034] Cetyl esters (INCI name), also called cetyl esters or cetyl esters, are ingredients commonly used in the cosmetics industry. They are plant-based waxes, generally derived from palm kernel oil or coconut oil. These cetyl esters are typically used to moisturize and soften the skin. Cetyl esters thus possess emollient and hydrating properties.

[0035] Cetyl esters are a mixture of esters of C14-C18 saturated fatty acids, preferably C14-C18, and C14-C18 alcohols, preferably C14-C16. Cetyl esters more particularly comprise a mixture of cetyl palmitate, cetyl stearate, myristyle myristate, myristyle stearate, cetyl myristate and stearyl stearate.

[0036] Association

[0037] The association according to the invention comprises, in particular, isocetyl stearoyl stearate as defined above and cetyl esters as defined above.

[0038] Isocetyl stearoyl stearate and cetyl esters are advantageously used in combination in an isocetyl stearoyl stearate / cetyl ester mass ratio of 5 / 1 to 1 / 5, in particular 5 / 1 to 1 / 1, preferably 4 / 1 to 2 / 1, in particular about 3.2 / 1.

[0039] The combination according to the invention is useful for strengthening skin protection against allergens (typically contact allergens), particularly allergens (typically contact allergens) containing a metal, and more specifically a heavy metal such as chromium and / or nickel. It acts as a shield against allergens.

[0040] The combination according to the invention is also useful for preventing allergic dermatitis, particularly allergic dermatitis due to a metal, and more specifically to a heavy metal such as chromium and / or nickel. Furthermore, according to another aspect, the invention relates to a combination of isocetyl stearoyl stearate and cetyl esters for use in preventing allergic dermatitis, particularly allergic dermatitis due to a metal, and more specifically to a heavy metal such as chromium and / or nickel.

[0041] The invention also relates to the use of the combination of isocetyl stearoyl stearate and cetyl esters to prevent allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel.

[0042] The invention also relates to the use of the combination of isocetyl stearoyl stearate and cetyl esters for the preparation of a drug to prevent allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel.

[0043] The invention also relates to a method for preventing allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel, comprising administering to a person in need an effective amount of a combination of isocetyl stearoyl stearate and cetyl esters.

[0044] Compositions

[0045] The compositions according to the invention comprise a combination as described in the invention. They enhance skin protection against allergens (typically contact allergens), particularly allergens containing metal, and more specifically heavy metals such as chromium and / or nickel. They act as a shield against allergens.

[0046] The compositions according to the invention are also useful for preventing allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly a heavy metal such as chromium and / or nickel.

[0047] Also, according to another aspect, the invention relates to a composition according to the invention for its use in preventing allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel.

[0048] The invention also relates to the use of a composition according to the invention to prevent allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel.

[0049] The invention also relates to the use of a composition according to the invention for the preparation of a drug to prevent allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel.

[0050] The invention also relates to a method of treatment to prevent allergic dermatitis, in particular allergic dermatitis due to a metal, and more particularly to a heavy metal such as chromium and / or nickel, comprising administering to a person in need an effective amount of a composition according to the invention.

[0051] According to one embodiment, the compositions according to the invention contain from 1% to 10%, in particular from 2% to 10%, in particular from 2% to 8%, more particularly from 4% to 8% of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

[0052] According to one embodiment, the compositions according to the invention contain from 0.1% to 10%, in particular from 0.5% to 8%, in particular from 1% to 6%, more particularly from 1.5% to 5%, and more particularly still from 1.5% to 3% of cetyl esters by weight relative to the total weight of the composition.

[0053] Isocetyl stearoyl stearate and cetyl esters are advantageously used in the composition in a mass ratio of isocetyl stearoyl stearate / cetyl esters ranging from 5 / 1 to 1 / 5, in particular from 5 / 1 to 1 / 1, preferably ranging from 4 / 1 to 2 / 1, in particular from about 3.2 / 1.

[0054] The compositions according to the invention further advantageously comprise at least one cosmetically or dermatologically acceptable excipient.

[0055] The compositions according to the invention are advantageously intended for topical application, particularly by application to the skin. They are therefore more specifically in a form suitable for topical application. The composition according to the invention can, in particular, be applied to sensitive, fragile, and / or reactive skin.

[0056] The compositions according to the invention may thus be presented in the forms which are usually known for topical administration, namely in particular lotions, milks, serums, balms, ointments, masks, creams, dispersions, gels, foams or sprays.

[0057] They can also be in solid form, such as a stick, or applied to the skin as an aerosol. These compositions may include an oily solution or an emulsion such as an oil-in-water emulsion, a water-in-oil emulsion, or a multi-emulsion.

[0058] The following example illustrates the invention without limiting its scope. EXAMPLE

[0059] The objective of this study was to evaluate the protective properties of isocetyl stearoyl stearate, cetyl esters, and the combination of these two ingredients against allergenic chromium and nickel compounds on the skin barrier. This effect was assessed by monitoring chromium and nickel compounds applied to skin previously treated with the studied formulations. Specifically, the rate and extent of in vitro skin absorption of chromium and nickel contained in an aqueous gel were evaluated after topical application of the tested formulations. The study was conducted on human skin mounted on static diffusion cells.

[0060] Method

[0061] The products used are:

[0062] - For the chromium test: potassium dichromate (KCO₃),

[0063] - For the nickel test: nickel sulfate hexahydrate (NiSCU.ôEEO).

[0064] Isocetyl stearoyl stearate and cetyl esters are solubilized in dimethicone to achieve the desired percentages, which are 6.4% for isocetyl stearoyl stearate and 2% for cetyl esters.

[0065] The percutaneous penetration study was conducted in accordance with the following guideline:

[0066] Directive SCCS / 0970 / 06: “Basic criteria for the in-vitro assessment of dermal absorption of cosmetic ingredients” (updated version of March 2006).

[0067] The biological model used for this study consists of human skin expiants isolated from cosmetic surgery (abdominoplasties) from 4 different donors.

[0068] The different characteristics of the model are summarized in Table 1 below.

[0069] [Table 1]

[0070] Topical application of the ingredients to the expiry is performed 1 hour before the chromium or nickel stress test, which consists of applying a potassium dichromate and nickel sulfate hexahydrate gel. The potassium dichromate and nickel sulfate hexahydrate gel is prepared as follows: Dissolve 1 g of nickel sulfate hexahydrate in 100 mL of potassium dichromate solution. Add the solution dropwise initially in an ice bath. Once the 100 mL has been added, while stirring, gradually add 0.7 g of xanthan gum.

[0071] The final gel has a nickel content of 2.23 mg / g and a chromium content of 4.33 mg / g.

[0072] 24 hours after application, the distribution of chromium or nickel is measured in the different compartments (stratum corneum, skin and receiving fluid) thus allowing the study of skin penetration.

[0073] All samples were analyzed by inductively coupled plasma mass spectrometry (ICP / MS).

[0074] The results of the compartmental distribution of chromium are presented in Table 2 below.

[0075] [Table 2]

[0076] ISS: isocetyl stearoyl stearate; CE: cetyl esters *p<0.05 versus untreated group

[0077] After 24 hours, 2.27 pg / cm 2 Chromium levels were found in the untreated control expiants. This value corresponds to the sum of the amounts found in the skin and in the receiving fluid. Similar results were observed after application of 6.4% isocetyl stearoyl stearate (ISS) or after application of 2% cetyl esters (CE) (see Table 2). In contrast, after application of the combination of the two ingredients, only 1.47 pg / cm² was found. 2Chromium is found in the skin and receptor fluid, this value being significantly lower than that found with the untreated control condition (p<0.05).

[0078] The combination of isocetyl stearoyl stearate and cetyl esters therefore makes it possible to significantly limit the passage of chromium into the skin.

[0079] The results of the compartmental distribution of nickel are presented in Table 3 below.

[0080] [Table 3]

[0081] ISS: isocetyl stearoyl stearate; CE: cetyl esters *p<0.05 versus untreated group. After 24 hours, 7.58 pg / cm² 2Chromium levels were found in the untreated control expungants. This value corresponds to the sum of the amounts found in the skin and in the receiving fluid. The bioavailability of nickel after application of 6.4% isocetyl stearoyl stearate or 2% cetyl esters tended to be lower, but without reaching a level of significance compared to the control group. As observed for chromium, the bioavailability of nickel after application of the combination of the two ingredients was significantly lower (see Table 3).

[0082] The combination of isocetyl stearoyl stearate and cetyl esters significantly limits the passage of nickel into the skin.

[0083] Isocetyl stearoyl stearate, tested at 6.4%, and cetyl esters, tested at 2%, showed no barrier effect against chromium or nickel when applied alone. However, surprisingly, the inventors demonstrated that, in combination, these two ingredients exhibited a barrier effect against chromium and nickel, significantly reducing the penetration of these pollutants into the skin. Bioavailability was thus reduced by 38% for chromium and by 72% for nickel thanks to the combination of isocetyl stearoyl stearate and cetyl esters.

[0084] The inventors thus highlight that the combination of isocetyl stearoyl stearate and cetyl esters protects the skin against contact allergens.

[0085] Bibliographic reference:

[0086] Thyssen and Menne, Chem. Res. Toxicol. 2010, 15, 23(2), 309-318.

Claims

DEMANDS 1. Non-therapeutic use of a combination of isocetyl stearoyl stearate and cetyl esters, wherein the cetyl esters are a mixture of C14-C18 saturated fatty acid esters and C14-C18 alcohols, to enhance skin protection against metal allergens, wherein the metal is a heavy metal.

2. Use according to claim 1, wherein the heavy metal is chromium and / or nickel.

3. Association consisting of isocetyl stearoyl stearate and cetyl esters in which the cetyl esters are a mixture of C14-C18 saturated fatty acid esters and C14-C18 alcohols, to prevent heavy metal allergic dermatitis.

4. Association for its use according to claim 3, wherein the heavy metal is chromium and / or nickel.

5. Non-therapeutic use of a cosmetic or dermatological composition comprising isocetyl stearoyl stearate and cetyl esters in which the cetyl esters are a mixture of C14-C18 saturated fatty acid esters and C14-C18 alcohols, to enhance skin protection against allergens comprising a metal, in which the metal is a heavy metal.

6. Use according to claim 5, wherein the heavy metal is chromium and / or nickel.

7. Use according to claim 5 or 6, characterized in that the composition further comprises at least one cosmetically or dermatologically acceptable excipient.

8. Use according to any one of claims 5 to 7, characterized in that the composition comprises from 1% to 10%, in particular from 2% to 10%, in particular from 2% to 8%, more particularly from 4% to 8% of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

9. Use according to any one of claims 5 to 8, characterized in that the composition comprises from 0.1% to 10%, in particular from 0.5% to 8%, in particular from 1% to 6%, more particularly from 1.5% to 5%, and more particularly still from 1.5% to 3% of cetyl esters by weight relative to the total weight of the composition.

10. Use according to any one of claims 5 to 9, characterized in that the composition is in a form suitable for topical application.

11. Cosmetic or dermatological composition comprising isocetyl stearoyl stearate and cetyl esters, wherein the cetyl esters are a mixture of saturated fatty acid esters in C14-C18 and C14-C18 alcohols, to prevent allergic dermatitis due to heavy metal.

12. Composition for use according to claim 11, wherein the heavy metal is chromium and / or nickel.

13. Composition for use according to claim 11 or 12, characterized in that it further comprises at least one cosmetically or dermatologically acceptable excipient.

14. Composition for use according to any one of claims 11 to 13, characterized in that it comprises from 1% to 10%, in particular from 2% to 10%, in particular from 2% to 8%, more particularly from 4% to 8% of isocetyl stearoyl stearate by weight relative to the total weight of the composition.

15. Composition for use according to any one of claims 11 to 14, characterized in that it comprises from 0.1% to 10%, in particular from 0.5% to 8%, in particular from 1% to 6%, more particularly from 1.5% to 5%, and more particularly still from 1.5% to 3% of cetyl esters by weight relative to the total weight of the composition.

16. Composition for its use according to any one of claims 11 to 15, characterized in that it is in a form suitable for topical application.

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